This invention relates to the repair of joints, which have been injured and/or been subjected to disorders such as osteoarthritis. More particularly, this invention relates to the repair of joints to preventing or reducing subchondral bone sclerosis in a joint, and to preventing damage to the articular cartilage in a joint, and to preventing or reducing the formation of osteophytes in a joint, by administering mesenchymal stem cells to a joint which is in need of repair.
Osteoarthritis is one of the most common diseases of the joint. There is radiological evidence of the disease in approximately 70% of individuals over 65 years, with a slightly higher incidence in females. In the age range of 45-65 years, the incidence approaches 30% of the population (American Academy of Orthopedic Surgeons, 1992). Osteoarthritis is a degenerative disease involving erosion of the articular surface at the ends of bones, leading ultimately to complete loss of the cartilage surface and exposure of the subchondral bone. These changes accompany the onset of severe symptoms including loss of motion, stiffness and joint pain. Articular cartilage, once damaged, does not demonstrate significant self-repair. What little tissue repair occurs is typically fibrous in nature and is an inadequate functional true substitute for articular cartilage. A variety of methods have been investigated to enhance the healing of defects in articular cartilage, with varying degrees of success.
Although osteoarthritis is a major disease affecting a large proportion of the population, the causative factors are unknown. Knee injuries involving the meniscus or the anterior cruciate ligament (ACL) significantly increase the development of radiographic gonarthrosis. Meniscal injury alone results in a 20-fold increase in the risk of developing osteoarthritis. In patients that suffer injury to the ACL or other ligaments in combination with meniscus rupture, there is a very high likelihood that osteoarthritis of the knee will develop. (Gillquist and Messner, Sports Med., Vol. 27, pgs. 143-156 (1999)).
Medial or lateral meniscectomy or ACL resection have been used as a means of creating instability in the knee joints leading to the development of osteoarthritic lesions of large animals such as the sheep (Ghosh, et al., Clin. Orthop., Vol. 252, pgs. 101-113, 1990; Uttle, et al., J. Rheumatol., Vol. 11, pgs. 2199-2209, 1997) and dog (for review see Brandt, Ann. N.Y. Acad. Sci., Vol. 732, pgs. 199-205, 1994). These animals, however, differ from humans with respect to the structure of the articular cartilage layer and subchondral bone and also in the mechanical properties of the tissue. The adult goat has the advantage of being active and having a structural and tissue organization in the stifle joint that compares well with the human knee. There are few reports in the literature demonstrating the use of the; goat as a model for human osteoarthritis. In an early study, involving 4 goats, transection of the anterior cruciate ligament resulted in focal defects on the condylar cartilage (Ho, et al., Invest. Radiol., Vol. 27, pgs. 84-90, 1992). In a more recent study, however, surgical transection of the cruciate ligament failed to produce osteoarthritic changes after 8 months in young, confined goats (Rorvik and Tiege, Acta. Vet. Scand., Vol. 37, pgs. 265-272, 1996).